Engineering osteochondral constructs through spatial regulation of endochondral ossification.

Eamon J Sheehy, Tatiana Vinardell, Conor T Buckley, Daniel J Kelly

Trinity Centre for Bioengineering, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland.

Acta biomaterialia 2013 Mar

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Chondrogenically primed bone marrow-derived mesenchymal stem cells (MSCs) have been shown to become hypertrophic and undergo endochondral ossification when implanted in vivo. Modulating this endochondral phenotype may be an attractive approach to engineering the osseous phase of an osteochondral implant. The objective of this study was to engineer an osteochondral tissue by promoting endochondral ossification in one layer of a bilayered construct and stable cartilage in the other. The top half of bilayered agarose hydrogels were seeded with culture expanded chondrocytes (termed the chondral layer) and the bottom half of the bilayered agarose hydrogels with MSCs (termed the osseous layer). Constructs were cultured in chondrogenic medium for 21days and thereafter were either maintained in chondrogenic medium, transferred to hypertrophic medium, or implanted subcutaneously into nude mice. This structured chondrogenic bilayered co-culture was found to enhance chondrogenesis in the chondral layer, appearing to help re-establish the chondrogenic phenotype that is lost in chondrocytes during monolayer expansion. Furthermore, the bilayered co-culture appeared to suppress hypertrophy and mineralization in the osseous layer. The addition of hypertrophic factors to the media was found to induce mineralization of the osseous layer in vitro. A similar result was observed in vivo where endochondral ossification was restricted to the osseous layer of the construct, leading to the development of an osteochondral tissue. This novel approach represents a potential new treatment strategy for the repair of osteochondral defects. Copyright © 2012 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Citation

Eamon J Sheehy, Tatiana Vinardell, Conor T Buckley, Daniel J Kelly. Engineering osteochondral constructs through spatial regulation of endochondral ossification. Acta biomaterialia. 2013 Mar;9(3):5484-92